1. Field of the Invention
The present invention relates to an antihypertensive agent comprising a Boysenberry seed extract as an active ingredient, and to a method for producing the antihypertensive agent. The invention also relates to a food and beverage product composition and a pharmaceutical product composition, which include the antihypertensive agent. Additionally, the invention relates to a food and beverage product composition comprising a Boysenberry seed extract.
2. Background Art
It is widely known that triggers, such as western-style eating habits, lack of exercise, stress, smoking and hereditary factors, cause so-called typical lifestyle-related diseases, that is, hypertension and hyperlipidemia (for example, hypercholesteremia and hypertriglyceridemia). Among them, hypertension has the highest prevalence rate and is a disease that needs urgent preventive strategies from a health economic aspect.
In general, to ameliorate hypertensive symptoms, there have been conducted pharmacotherapies with diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor antagonists, sympatholytic drugs, vasodilators or the like. These pharmacotherapies, however, have been reported to cause various side effects such as stomach malaise, diarrhea, and angioedema. Accordingly, there has been a social demand for the prevention and amelioration of hypertension using foods that are ordinarily edible with few side effects.
Boysenberry (Rubus ursinus×idaeus or Rubus loganobaccus and Rubus baileyanus Britt.) is said to be a crossbreed between blackberry and raspberry or a selected species of mutant wild berry species and is popular in Europe and America.
Regarding the functionality of Boysenberry-derived components, for example, an article (Kiyoko Kubomura, “Boysenberry as a Functional Food Ingredient”, Journal of the Japan Association for the Integrated Study of Dietary Habits, vol. 16, No. 1, pp. 44-49, 2005) describes that Boysenberry contains a large amount of polyphenolic components with excellent antioxidant effect, such as anthocyanins and ellagic acid. The article predicts that anthocyanins included in fruits and leaves of Boysenberry are expected to have aging-preventing effect, cardiovascular function-protecting effect, diabetic exacerbation-inhibiting effect, hepatic damage-preventing effect, and the like. In addition, Japanese Patent Laid-Open Publication No. 2008-156306 has disclosed that a Boysenberry fruit-derived component can exhibit cancer-inhibiting effect. Furthermore, Japanese Patent Laid-Open Publication No. 2010-254590 has disclosed that Boysenberry-derived components, particularly a Boysenberry juice-derived component can exhibit pancreatic lipase-inhibiting effect.
In addition, WO 2010/092941 has disclosed that by combining a condensed tannin oligomer component, such as at least one of proanthocyanidins from dimer to tridecamer that are Boysenberry fruit-derived components and at least one organic acid, a vasodilator effect and an antihypertensive effect can be exhibited. Furthermore, an article (Ryo Furuuchi et al., “Analysis of proanthocyanidins in Boysenberry juice and the vasorelaxant effect in vitro”, Proceedings of the 64th Annual Meeting of Japan Society of Nutrition and Food Science, 2010) has disclosed that a proanthocyanidin fraction from a Boysenberry fruit extract has a vasorelaxant effect and a combination thereof with citric acid as an organic acid can exhibit a strong vasorelaxant effect.
However, those articles have not described that Boysenberry extract alone has high antihypertensive activity. Additionally, there has been conducted no investigation focusing on Boysenberry seed.
Proanthocyanidins are a group of polyphenols contained in plants and fruits and also called “condensed tannins” or “nonhydrolyzable tannins”. Proanthocyanidins are structurally a group of condensed polymerized substances consisting of flavan-3-ols as constituent units and are known to be present as various structural components depending on the structure of the constituent unit, the position of bonding, and the degree of polymerization. Depending on the differences in constituent unit, proanthocyanidins are classified into three subclasses, namely, procyanidins (condensed polymerized substances such as catechin, epicatechin, and epicatechin gallate), prodelphinidins (condensed polymerized substances such as gallocatechin, epigallocatechin, and epigallocatechin gallate), and propelargonidins (condensed polymerized substances such as afzelechin and epiafzelechin). Depending on the differences in bonding position, proanthocyanidins are largely divided into B type (a carbon-carbon bond between the constituent units is only 4β→8 or 4β→6) and A type (a carbon-carbon bond between the constituent units has at least one of 4β→8 and 2β→O→7 or 4β→6 and 2β→O→7).
It is known that components contained in plants and the structures and contents of the components largely vary depending on the kinds and tissue sites of the plants. In fact, regarding proanthocyanidins also, there is a report that proanthocyanidins contained in plants have significantly different unique structures, depending on the kinds of the plants from which they are derived. Such differences influence on health function and oral absorbability (M. Monagas, C. Gomez-Cordoves, B. Bartolome, O. Laureano, J. M. Ricardo da Silva, Monomeric, oligomeric, and polymeric flavan-3-ol composition of wines and grapes from Vitis vinifera L. Cv. Graciano, Tempranillo, and Cabernet Sauvignon. J. Agric. Food Chem. 2003, 51, p. 6475-6481).
When considering the bioavailability of proanthocyanidin, oral absorbability is concerned with whether proanthocyanidin can effectively exhibit its function or not, which thus has an extremely important meaning. Studies on oral absorbability of various kinds of proanthocyanidins have reported that oligomers with a low degree of polymerization are efficiently orally absorbed (see R. R. Holt, S. A. Lazarus, M. C. Sullards, Q. Y. Zhu, D. D. Schramm, J. F. Hammerstone, C. G. Fraga, H. H. Schmitz and C. L. Keen, Procyanidin dimer B2 [epicatechin-(4β-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am. J. Clin. Nutr. 2002, 76, p. 798-804. T. Shoji, S. Masumoto, N. Moriichi, H. Akiyama, T. Kanda, Y. Ohtake, Y. Goda. Apple procyanidin oligomers absorption in rats after oral administration: Analysis of procyanidins in plasma using the porter method and High-Performance Liquid Chromatography/Tandem Mass Spectrometry. J. Agric. Food Chem. 2006, 54, p. 884-892).
Japanese Patent Laid-Open Publication No. 2003-212783 has disclosed antihyperglycemic and antihypertensive effects by proanthocyanidin contained in an extract obtained from a grape seed squeezed juice. It has described that a preferable proanthocyanidin has a molecular weight of 3000 or more (a degree of polymerization: 6.7 or more). However, its component and structure were different from those in proanthocyanidin found in Boysenberry seed and the effect of its activity was low.
Accordingly, there has been no report on the component, structure, and oral absorbability of Boysenberry seed-derived proanthocyanidin.